Cargando…

A diversity-oriented rhodamine library for wide-spectrum bactericidal agents with low inducible resistance against resistant pathogens

Antimicrobial resistance is a public health emergency and warrants coordinated global efforts. Challenge is that no alternative molecular platform has been identified for discovery of abundant antimicrobial hit compounds. Xanthene libraries have been screened for bioactive compounds. However, the po...

Descripción completa

Detalles Bibliográficos
Autores principales: Luo, Xiao, Qian, Liujia, Xiao, Yansheng, Tang, Yao, Zhao, Yang, Wang, Xia, Gu, Luyan, Lei, Zuhai, Bao, Jianming, Wu, Jiahui, He, Tingting, Hu, Fupin, Zheng, Jing, Li, Honglin, Zhu, Weiping, Shao, Lei, Dong, Xiaojing, Chen, Daijie, Qian, Xuhong, Yang, Youjun
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6335415/
https://www.ncbi.nlm.nih.gov/pubmed/30651565
http://dx.doi.org/10.1038/s41467-018-08241-3
_version_ 1783387882571956224
author Luo, Xiao
Qian, Liujia
Xiao, Yansheng
Tang, Yao
Zhao, Yang
Wang, Xia
Gu, Luyan
Lei, Zuhai
Bao, Jianming
Wu, Jiahui
He, Tingting
Hu, Fupin
Zheng, Jing
Li, Honglin
Zhu, Weiping
Shao, Lei
Dong, Xiaojing
Chen, Daijie
Qian, Xuhong
Yang, Youjun
author_facet Luo, Xiao
Qian, Liujia
Xiao, Yansheng
Tang, Yao
Zhao, Yang
Wang, Xia
Gu, Luyan
Lei, Zuhai
Bao, Jianming
Wu, Jiahui
He, Tingting
Hu, Fupin
Zheng, Jing
Li, Honglin
Zhu, Weiping
Shao, Lei
Dong, Xiaojing
Chen, Daijie
Qian, Xuhong
Yang, Youjun
author_sort Luo, Xiao
collection PubMed
description Antimicrobial resistance is a public health emergency and warrants coordinated global efforts. Challenge is that no alternative molecular platform has been identified for discovery of abundant antimicrobial hit compounds. Xanthene libraries have been screened for bioactive compounds. However, the potentially accessible chemistry space of xanthene dyes is limited by the existing xanthene synthesis. Herein we report a mild one-step synthesis, which permits late-stage introduction of a xanthene moiety onto i.e. natural products, pharmaceuticals, and bioactive compounds and construction of a focused library of rhodamine dyes exhibiting facile functional, topographical and stereochemical diversity. In vitro screening yields 37 analogs with mid-to-high bactericidal activity against WHO priority drug-resistant pathogens. These findings suggest that synthetic dye libraries exhibiting high structural diversity is a feasible chemical space combating antibacterial resistance, to complement the natural sources.
format Online
Article
Text
id pubmed-6335415
institution National Center for Biotechnology Information
language English
publishDate 2019
publisher Nature Publishing Group UK
record_format MEDLINE/PubMed
spelling pubmed-63354152019-01-18 A diversity-oriented rhodamine library for wide-spectrum bactericidal agents with low inducible resistance against resistant pathogens Luo, Xiao Qian, Liujia Xiao, Yansheng Tang, Yao Zhao, Yang Wang, Xia Gu, Luyan Lei, Zuhai Bao, Jianming Wu, Jiahui He, Tingting Hu, Fupin Zheng, Jing Li, Honglin Zhu, Weiping Shao, Lei Dong, Xiaojing Chen, Daijie Qian, Xuhong Yang, Youjun Nat Commun Article Antimicrobial resistance is a public health emergency and warrants coordinated global efforts. Challenge is that no alternative molecular platform has been identified for discovery of abundant antimicrobial hit compounds. Xanthene libraries have been screened for bioactive compounds. However, the potentially accessible chemistry space of xanthene dyes is limited by the existing xanthene synthesis. Herein we report a mild one-step synthesis, which permits late-stage introduction of a xanthene moiety onto i.e. natural products, pharmaceuticals, and bioactive compounds and construction of a focused library of rhodamine dyes exhibiting facile functional, topographical and stereochemical diversity. In vitro screening yields 37 analogs with mid-to-high bactericidal activity against WHO priority drug-resistant pathogens. These findings suggest that synthetic dye libraries exhibiting high structural diversity is a feasible chemical space combating antibacterial resistance, to complement the natural sources. Nature Publishing Group UK 2019-01-16 /pmc/articles/PMC6335415/ /pubmed/30651565 http://dx.doi.org/10.1038/s41467-018-08241-3 Text en © The Author(s) 2019 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Luo, Xiao
Qian, Liujia
Xiao, Yansheng
Tang, Yao
Zhao, Yang
Wang, Xia
Gu, Luyan
Lei, Zuhai
Bao, Jianming
Wu, Jiahui
He, Tingting
Hu, Fupin
Zheng, Jing
Li, Honglin
Zhu, Weiping
Shao, Lei
Dong, Xiaojing
Chen, Daijie
Qian, Xuhong
Yang, Youjun
A diversity-oriented rhodamine library for wide-spectrum bactericidal agents with low inducible resistance against resistant pathogens
title A diversity-oriented rhodamine library for wide-spectrum bactericidal agents with low inducible resistance against resistant pathogens
title_full A diversity-oriented rhodamine library for wide-spectrum bactericidal agents with low inducible resistance against resistant pathogens
title_fullStr A diversity-oriented rhodamine library for wide-spectrum bactericidal agents with low inducible resistance against resistant pathogens
title_full_unstemmed A diversity-oriented rhodamine library for wide-spectrum bactericidal agents with low inducible resistance against resistant pathogens
title_short A diversity-oriented rhodamine library for wide-spectrum bactericidal agents with low inducible resistance against resistant pathogens
title_sort diversity-oriented rhodamine library for wide-spectrum bactericidal agents with low inducible resistance against resistant pathogens
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6335415/
https://www.ncbi.nlm.nih.gov/pubmed/30651565
http://dx.doi.org/10.1038/s41467-018-08241-3
work_keys_str_mv AT luoxiao adiversityorientedrhodaminelibraryforwidespectrumbactericidalagentswithlowinducibleresistanceagainstresistantpathogens
AT qianliujia adiversityorientedrhodaminelibraryforwidespectrumbactericidalagentswithlowinducibleresistanceagainstresistantpathogens
AT xiaoyansheng adiversityorientedrhodaminelibraryforwidespectrumbactericidalagentswithlowinducibleresistanceagainstresistantpathogens
AT tangyao adiversityorientedrhodaminelibraryforwidespectrumbactericidalagentswithlowinducibleresistanceagainstresistantpathogens
AT zhaoyang adiversityorientedrhodaminelibraryforwidespectrumbactericidalagentswithlowinducibleresistanceagainstresistantpathogens
AT wangxia adiversityorientedrhodaminelibraryforwidespectrumbactericidalagentswithlowinducibleresistanceagainstresistantpathogens
AT guluyan adiversityorientedrhodaminelibraryforwidespectrumbactericidalagentswithlowinducibleresistanceagainstresistantpathogens
AT leizuhai adiversityorientedrhodaminelibraryforwidespectrumbactericidalagentswithlowinducibleresistanceagainstresistantpathogens
AT baojianming adiversityorientedrhodaminelibraryforwidespectrumbactericidalagentswithlowinducibleresistanceagainstresistantpathogens
AT wujiahui adiversityorientedrhodaminelibraryforwidespectrumbactericidalagentswithlowinducibleresistanceagainstresistantpathogens
AT hetingting adiversityorientedrhodaminelibraryforwidespectrumbactericidalagentswithlowinducibleresistanceagainstresistantpathogens
AT hufupin adiversityorientedrhodaminelibraryforwidespectrumbactericidalagentswithlowinducibleresistanceagainstresistantpathogens
AT zhengjing adiversityorientedrhodaminelibraryforwidespectrumbactericidalagentswithlowinducibleresistanceagainstresistantpathogens
AT lihonglin adiversityorientedrhodaminelibraryforwidespectrumbactericidalagentswithlowinducibleresistanceagainstresistantpathogens
AT zhuweiping adiversityorientedrhodaminelibraryforwidespectrumbactericidalagentswithlowinducibleresistanceagainstresistantpathogens
AT shaolei adiversityorientedrhodaminelibraryforwidespectrumbactericidalagentswithlowinducibleresistanceagainstresistantpathogens
AT dongxiaojing adiversityorientedrhodaminelibraryforwidespectrumbactericidalagentswithlowinducibleresistanceagainstresistantpathogens
AT chendaijie adiversityorientedrhodaminelibraryforwidespectrumbactericidalagentswithlowinducibleresistanceagainstresistantpathogens
AT qianxuhong adiversityorientedrhodaminelibraryforwidespectrumbactericidalagentswithlowinducibleresistanceagainstresistantpathogens
AT yangyoujun adiversityorientedrhodaminelibraryforwidespectrumbactericidalagentswithlowinducibleresistanceagainstresistantpathogens
AT luoxiao diversityorientedrhodaminelibraryforwidespectrumbactericidalagentswithlowinducibleresistanceagainstresistantpathogens
AT qianliujia diversityorientedrhodaminelibraryforwidespectrumbactericidalagentswithlowinducibleresistanceagainstresistantpathogens
AT xiaoyansheng diversityorientedrhodaminelibraryforwidespectrumbactericidalagentswithlowinducibleresistanceagainstresistantpathogens
AT tangyao diversityorientedrhodaminelibraryforwidespectrumbactericidalagentswithlowinducibleresistanceagainstresistantpathogens
AT zhaoyang diversityorientedrhodaminelibraryforwidespectrumbactericidalagentswithlowinducibleresistanceagainstresistantpathogens
AT wangxia diversityorientedrhodaminelibraryforwidespectrumbactericidalagentswithlowinducibleresistanceagainstresistantpathogens
AT guluyan diversityorientedrhodaminelibraryforwidespectrumbactericidalagentswithlowinducibleresistanceagainstresistantpathogens
AT leizuhai diversityorientedrhodaminelibraryforwidespectrumbactericidalagentswithlowinducibleresistanceagainstresistantpathogens
AT baojianming diversityorientedrhodaminelibraryforwidespectrumbactericidalagentswithlowinducibleresistanceagainstresistantpathogens
AT wujiahui diversityorientedrhodaminelibraryforwidespectrumbactericidalagentswithlowinducibleresistanceagainstresistantpathogens
AT hetingting diversityorientedrhodaminelibraryforwidespectrumbactericidalagentswithlowinducibleresistanceagainstresistantpathogens
AT hufupin diversityorientedrhodaminelibraryforwidespectrumbactericidalagentswithlowinducibleresistanceagainstresistantpathogens
AT zhengjing diversityorientedrhodaminelibraryforwidespectrumbactericidalagentswithlowinducibleresistanceagainstresistantpathogens
AT lihonglin diversityorientedrhodaminelibraryforwidespectrumbactericidalagentswithlowinducibleresistanceagainstresistantpathogens
AT zhuweiping diversityorientedrhodaminelibraryforwidespectrumbactericidalagentswithlowinducibleresistanceagainstresistantpathogens
AT shaolei diversityorientedrhodaminelibraryforwidespectrumbactericidalagentswithlowinducibleresistanceagainstresistantpathogens
AT dongxiaojing diversityorientedrhodaminelibraryforwidespectrumbactericidalagentswithlowinducibleresistanceagainstresistantpathogens
AT chendaijie diversityorientedrhodaminelibraryforwidespectrumbactericidalagentswithlowinducibleresistanceagainstresistantpathogens
AT qianxuhong diversityorientedrhodaminelibraryforwidespectrumbactericidalagentswithlowinducibleresistanceagainstresistantpathogens
AT yangyoujun diversityorientedrhodaminelibraryforwidespectrumbactericidalagentswithlowinducibleresistanceagainstresistantpathogens